Leukemia is a disease in which immature hematopoietic stem cells are developed and proliferate abnormally in bone marrow. Leukemia is classified into 4 types (acute myeloid leukemia, chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia) depending on the type of developed cells and the proliferation rate thereof. Myelodysplastic syndrome is also included in leukemia because of its similarity and correlation in findings.
Acute leukemia is a disease in which hematopoietic stem cells and/or progenitor cells are developed and only specific cells proliferate as leukemia cells. On the other hand, chronic leukemia is a disease in which stem cells per se proliferate autonomously but maintain ability to differentiate into mature cells, and only the cells originated from a certain clone proliferate autonomously. Myelodysplastic syndrome is a disease in which hematopoietic stem cells acquire genetic abnormality a posteriori and thereby presenting cytopenia and/or dysplasia in hematopoietic system.
Although the cause of leukemia has not been fully clarified, it is thought that the cause is a genetic abnormality in hemocytes, radiation or the like.
Although the patients of leukemia receive therapy with heavy burdens such as chemotherapy by antitumor agents, bone marrow transplantation or the like, the vital prognosis of the patient is poor. QOL is often disturbed seriously by side effects and/or complications, and thus a need for the therapy aiming at improving the vital prognosis and QOL is increasing year by year.
Examples of the agent used in the pharmacotherapy of leukemia include alkylating agents, antimetabolites, anthracycline antibiotics, plant alkaloids, steroids, biologics such as interferons and the like, molecular target inhibitors, and immunosuppressants. Such agents are used individually or several of the agents are used in combination. However, agents now being used have many problems in use such as toxicity and low effectiveness.
Thus, the therapeutic agents for leukemia now existing are not fully satisfactory with respect to effects thereof and reduction of side effects.
On the other hand, Patent Literature 1 discloses a use of the compounds represented by the below-described Formula:
(wherein Ar represents substituted phenylene or the like, L represents —S(O)2— or the like, X represents a bond or the like, Z represents COOH or the like, R2, R3, R4 represent hydrogen or the like, R5 represents —C2-10 alkenyl-aryl-NRdRe-heteroaryl-(Rd, Re represent hydrogen, C1-10 alkyl) or the like, R6 represents hydrogen or the like), which can be considered to be structurally similar to the compounds contained as an effective ingredient in the present invention, for the therapy of asthma, allergic rhinitis, multiple sclerosis, arteriosclerosis, and inflammatory bowel disease. However, the compounds whose uses mentioned above are disclosed in the publication are structurally different from the compounds in the present invention in that the disclosed compounds are characterized in that Ar in the Formula is substituted with aminoalkyl structure (R1LN(R2)CHR4—: R1 represents substituted aryl or the like). Moreover, the therapeutic or prophylactic effect on leukemia according to the present invention is not disclosed at all. Furthermore, concrete data which demonstrate the therapeutic effect on asthma, allergic rhinitis, multiple sclerosis, arteriosclerosis, and inflammatory bowel disease are not described, therefore the publication fails to fully disclose that the compounds really have the effect mentioned therein.
In claims of Patent Literatures 2 and 3, use of the compounds represented by the Formula:X-Y-Z-Aryl-A-B(wherein X represents a 6-membered aromatic ring comprising two nitrogen atoms or the like, Y represents —C0-6 alkylene-NC1-10 alkyl-C0-6 alkylene- or the like, Z represents a bond or the like, Aryl represents a 6-membered aromatic ring, A represents —(CH2)C═C(CH2)n-(n=0-6) or the like, B represents —CH (substituted aryl-carbonylamino)CO2H or the like), which includes the compounds in the present invention, as a bone resorption inhibitor and platelet aggregation inhibitor is described. However, the compounds in the present invention are not concretely described in the publications. The use disclosed therein is also totally different from that of in the present invention. The therapeutic or prophylactic effect on leukemia according to the present invention is not suggested at all.
Patent Literature 4, which was published after the priority date of the present application, discloses a compound which is contained as an effective ingredient in the present invention and use thereof for therapy of inflammatory bowel disease. However, the therapeutic or prophylactic effect on leukemia according to the present invention is not disclosed at all.
Patent Literature 1: WO 99/26923
Patent Literature 2: WO 95/32710
Patent Literature 3: WO 94/12181
Patent Literature 4: WO 2006/068213